tbuckley/cabot-search huggingface dataset:
Abstract 15274: Pediatric Valved Conduit From Biological Engineering in the Growing Lamb Model
Authors: Zeeshan Syedain, Matt Lahti, Bee Haynie, James Berry, Richard W Bianco, Robroy MacIver, Robert Tranquillo
Journal: Circulation (2022)

Introduction: A valved conduit with growth potential for pediatric patients remains an unmet need. Here we present a novel valved conduit with growth potential based on initial data in a growing lamb model. The valve is constructed from three biologically-engineered tubes of acellular collagenous matrix possessing somatic growth potential (Syedain et al., Nat Comms, 2016) using resorbable suture with each tube contributing to create a “leaflet” (Syedain et al, Sci Transl Med, 2021). This tri-tube valve previously demonstrated growth over 52 weeks when implanted interpositionally in the pulmonary artery. Methods: In this study, a fourth tube of the same matrix is placed around the tri-tube valve to create a tubular valved conduit. The inlet segment is cut diagonally to allow for direct attachment to the myocardium, emulating a clinical repair (see figure). Results: The first two lambs to date implanted in this study exhibited normal leaflet function, a pressure gradient less than 5mmHg without regurgitation or dilatation of the conduit at 12-week echocardiography (see figure). During this time the animal’s weight increased from 34±2kg to 48±1kg. The inflow pattern with this myocardial implantation was more uniform than in the previous study that used a pulmonary artery interposition implant of the just the valve (with no conduit). Discussion: Demonstrating integration of the conduit’s matrix to the myocardium is a key step toward a clinical trial. Previous pulmonary interposition implants of the valve, while achieving integration with the adjacent artery prior to dissolution of the Maxon suture (50% loss of tensile strength in ~3 weeks, complete by ~26 weeks), did not establish this clinically relevant point of myocardial integration. Conclusion: The preliminary finding is that the valved conduit exhibits excellent function at 12 weeks in the growing lamb and integration of the conduit’s matrix with the valve annulus-myocardium will likely occur. Funding: R01 HL107572
Abstract 15478: Obscure Back Pain - A Case of Spontaneous Retroperitoneal Bleed
Authors: Zauraiz Anjum, Saif ur Rehman, Ayesha Javed, Hongli Liu, Devesh Rai, Abdul Jawwad Samdani, Shaharyar Ali, Elizabeth Lee, Soidjon Khodjaev, Scott Feitell, Vishal Parikh
Journal: Circulation (2022)

Introduction: We present a case of spontaneous retroperitoneal bleed that presented as back pain until it required multiple transfusions. Case presentation: A 66-year-old gentleman with past medical history of only dyslipidemia, presented with chest pain and was found to have an anterior wall ST-elevation myocardial infarction. He underwent stenting to proximal LAD and was found to be in cardiogenic shock with elevated biventricular filling pressures and ejection fraction of 5-10%. IABP was inserted, which had to be upgraded to axillary Impella 5.5 the next day, and LVAD workup was initiated. He gradually improved with decreasing Impella needs when he started complaining of back pain 5 days into his admission. At the same time, his Impella requirements started to go up. He went on to develop sweating, pallor &amp; hemodynamic compromise. Since he was on anticoagulation due to Impella, a CT scan was obtained, which showed a spontaneous left-sided retroperitoneal bleed (F1) (IABP had been on the right side) and drop in hemoglobin from 15.8 mg/dl on admission to 7.2 mg/dl. He went on to develop hemorrhagic shock requiring massive blood product transfusion with subsequent vessel embolization by interventional radiology. Afterwards, he continued to improve, and Impella was eventually removed. Later in the course, he had another drop in hemoglobin &amp; was taken back for CT, which showed expanding retroperitoneal hematoma (F2). Hematology team was consulted due to 2 spontaneous bleeds; however, no underlying bleeding disorder was suspected. He stabilized; was weaned off of Impella and, was subsequently discharged on milrinone infusion. Conclusions: We conclude that providers highly suspect retroperitoneal bleeds in the proper clinical setting for optimum patient care.
Abstract 15753: Comparative Transcriptomics Analysis of Histone (De)acetylases and Cardiac Ion Channels in Human Induced Pluripotent Stem-Cell-Derived Cardiomyocytes vs. the Adult Human Heart
Authors: Maria R Pozo, Michael P Pressler, Emilia Entcheva
Journal: Circulation (2022)

Epigenetic regulation is critical for cardiac electrophysiology and pathology. Epigenetic modulators, such as histone deacetylases (HDACs) and histone acetyltransferases (HATs) are known master regulators of gene expression. Recently, novel pharmacological agents, HDAC inhibitors, have been developed as treatments for cancer and immune diseases. The effects of HDAC inhibitors on cardiac ion channels (ICs) are of great interest. To exert specific gene modulation, we used small interfering RNAs against the known HDACs, including sirtuins, and deployed them in human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs). Follow-up RNAseq data (n = 61) were compared to identically processed and normalized RNAseq data from human left ventricle (LV) from the GTEx database (n = 84). Gene expression of cardiac ICs displayed similar patterns, with some differences. For example, hiPSC-CMs showed upregulated CACNA1C, SLC8A1 and downregulated KCNJ2 and RYR2 compared to the adult LV, most of which are known distinctions (Fig. 1A). Correlative analysis (Fig. 1B) and partial least square regression models helped visualize links between HDACs/HATs, key transcription factors (TFs) and cardiac ICs. Powerful TFs, including MEF2A, GATA4, 6 exerted positive effect on ICs in hiPSC-CM and the adult LV. In the hiPSC-CMs, HDAC1, HDAC10 and SIRT6 were found to be the strongest predictors of the expression of individual cardiac ICs, as revealed by permutation importance. Further studies will involve determination of the role of different cell types using single-cell sequencing data from the adult LV. Our analysis offers new insights about the role of epigenetic modifiers on cardiac electrophysiology and informs the utility of hiPSC-CM as a scalable, experimental model for cardiotoxicity testing of HDAC inhibitors.
Abstract 15338: The Essential Role of Fatty-Acid Binding Protein 3 in Endothelial Function
Authors: Hien Chi Nguyen, Shuhan Bu, David Michels, Sepideh Nikfarjam, Berk Rasheed, Mohammad Qadura, Krishna Singh
Journal: Circulation (2022)

Background: The endothelium lines blood vessel’s inner walls and interacts directly with the circulation, systemically influencing whole-body physiology through endothelial function. Fatty acid binding protein 3 (FABP3), abundant in myocardiocytes, serve as effective cardiac injury’s biomarkers when presented in circulation. Our lab has preliminary found that endothelial cells (ECs) express FABP3. The role of FABP3 in endothelial function and FABP3 exposure’s effects on ECs are unknown. Objective: Evaluate FABP3’s role in endothelial dysfunction. Method: Human umbilical vein endothelial cells (HUVECs) were grown under cell culture standards (370 C, 5% CO2) prior to treatment by lipopolysaccharide (LPS). FABP3 expression in treated HUVECs was evaluated by qPCR. Next, FABP3-silencing RNAs were transfected into HUVECs to knock-down FABP3 for 24 hours. HUVECs were also exposed to recombinant FABP3 as a gain of function model. HUVECs were then treated with LPS for 24 hours before subjected to molecular/phenotypic evaluation for aspects of endothelial function (migration, proliferation, angiogenesis, inflammation). The Delta-Ct method and One-way ANOVA with Tukey (HSD) test were used to analyze data from qPCR and comparisons between treatment groups, respectively; p-value &lt; 0.05 is considered significant. Results: 1) FABP3 is basally expressed in ECs, 2) LPS upregulated endothelial FABP3 expression; 3) loss of FABP3 protected ECs against LPS-induced endothelial dysfunction; FABP3 exposure exacerbated LPS-induced inflammation; 4) loss of FABP3 protects ECs against LPS-induced stress by promoting cell survival, anti-inflammatory and pro-angiogenic pathways. Conclusions: We identified the novel and basal expression of FABP3 in ECs and demonstrated that FABP3 influences endothelial function at both the molecular and phenotypic levels under stress in vitro. Loss- and gain- of endothelial FABP3 ameliorates and exacerbates LPS-induced endothelial dysfunction, respectively, by affecting cell survival and inflammatory and angiogenic pathways. Our findings suggest that circulating FABP3 may be detrimental to the endothelium; therefore, therapies aimed at inhibiting FABP3 may improve endothelial function in myocardial injury.
Abstract 15673: AI-Enabled Prediction of Bleeding in Patients Supported on Extracorporeal Membrane Oxygenation
Authors: Peta M Alexander, Shelly DeForte, Sally Dufek, Mitchell Gauthier, Jeffrey Geppert, Jessily Ramirez, Michael Riedl, William White, Jonathan Bickel, Arash Nemati Hayati, Lynn A Sleeper, Ravi R Thiagarajan, Kathy J Jenkins
Journal: Circulation (2022)

Introduction: Clinical data within the electronic health record (EHR) combined with artificial intelligence (AI) and machine learning (ML) offer the promise of rapid advancement of knowledge at the point of care. Hypothesis: We hypothesized that aggregating clinical data with preservation of relational elements will yield a more precise and less biased representation of patient data for predictive analytics. We leveraged these data to predict clinically significant bleeding in the ECMO-supported population. Methods: The data of children 0-19 years managed on ECMO for first run cardiac indications in a single center between 1/2010-12/2020 were analyzed. Bleeding Day was defined as any 24-hour period which included pulmonary, gastrointestinal, intracranial or surgical wound hemorrhage, and/or surgical intervention or Factor VIIa administration for hemorrhage control. EHR data documenting the ECMO episode and embedding relational elements were used to inform 1) a multivariable logistic regression model matching a previously- performed analysis using manually extracted data [1], and 2) a feature-limited graph neural network (GNN) model of bleeding. Results: There were 272 patients supported with ECMO for total 2,012 days which informed the analysis, with median age 0.4 [IQR 0.03, 3.30] years, 56% male and 14% of days including a bleeding event. Direct comparison of the EHR-derived logistic regression model with previously published manual results are presented in Table 1. Inclusion of the EHR-derived covariates in a GNN model achieved similar operating characteristics. Conclusions: EHR-derived AI-prediction models of bleeding in this complex patient population are at least as accurate as models with manual data and traditional statistical analysis, but with a known pathway to potentially more accurate predictions. This methodology can be replicated to other conditions, allowing rapid insights towards a learning healthcare system.
Abstract 15255: Clinical Risk Factors for Infective Endocarditis in Patients With Staphylococcus Aureus Bacteremia and the Diagnostic Utility of Transesophageal Echocardiogram
Authors: Syeda Zaidi, Umair Khan, Harris Majeed, Erick Lopez, Manesh Kumar Gangwani, Davood Tofighi, Abu Baker Sheikh, Veena Raizada, PAUL ANDRE, Rahul Shekhar, Shazib Sagheer
Journal: Circulation (2022)

Background: Approximately 25% of patients with staphylococcus aureus bacteremia (SAB) develop infective endocarditis (IE), which has a consequent mortality of 46%. Current guidelines recommend routine transthoracic echocardiography (TTE) for patients with SAB; transesophageal echocardiogram (TEE) is reserved for those patients in whom initial TTE is negative and clinical suspicion for IE remains high. We sought to elucidate high risk features of SAB associated with the development of IE that warrant a TEE after a negative TTE. Methods: This retrospective study included 213 patients who were diagnosed with SAB at the University of New Mexico Hospital between 2010-2020. A pre-determined list of clinical risk factors along with TTE and TEE status was extracted from the electronic medical record (Table 1). Our primary outcome was the development of IE in patients with SAB. Multivariate logistic regression analysis was used to identify clinical risk factors for IE. Sensitivity and specificity of TTE and TEE was also calculated (Table 1). Results: Out of 213 patients with SAB, 68 patients met diagnostic criteria for infectious endocarditis. Most patients (n=209) underwent TTE and 117 patients underwent subsequent TEE. Initial TTE was diagnostic in 42 patients with a sensitivity of 63% and specificity of 94%; 45 patients had a diagnostic TEE with a sensitivity of 83% and specificity of 98%. Multivariate analysis showed significantly increased risk of IE in patients who had a permanent pacemaker (aOR 32.3, CI 5.23 - 281, p&lt;0.001) or a persistent fever (aOR 6.97, CI 2.42 - 21.0, P&lt;0.001). Conclusions: The routine use of TEE in patients with SAB for the diagnosis of IE may not be necessary and introduces unnecessary procedural risk. Based on our analysis, we recommend that SAB patients with a permanent pacemaker (or other intracardiac prosthetic) or a persistent fever despite appropriate antibiotic therapy be screened with TEE when initial TTE is negative.
Abstract 15379: Syncope and Pre-Syncope on the Exercise Test
Authors: Ibolya Csecs, Maria Barillas, Andres F Garzona-Navas, Amanda Bonikowske, Thomas G Allison
Journal: Circulation (2022)

Background: Data on the occurrence of syncope and presyncope with hemodynamic instability during graded exercise test (GXT) are limited. Methods: We reviewed the Mayo Integrated Stress Center database for non-imaging GXTs performed between January 2006 and December 2010 and registered syncopic/presyncopic episodes. Electronic medical records were reviewed for clinical information, outcomes, and mortality. SAS was used to provide background statistics. Results: During the study period, a total of 40,715 GXTs were performed on 33,885 unique patients, including 16,306 (40.0%) GXTs on patients with known cardiovascular disease (CVD). High risk for cardiac syncope is defined as prior cardiac arrest/ventricular tachycardia, ischemic cardiomyopathy, implanted defibrillator, history of atrial fibrillation, sotalol, amiodarone, LQTS, HOCM, aortic stenosis was identified in 3263 patients (6.0%), while risk factors for non-cardiac syncope (POTS, history of dizziness/spells/syncope, rest SBP &lt; 100 mmHg, age ≥ 80 years, female age &lt; 30 years, beta blocker use) were found in 15,925 patients (39.1%). Despite the presence of so many patients at risk, only 8 episodes of syncope occurred (0.020% per test; 0.023% per individual patient). Another 5 episodes of near-syncope with documented hypotension were aborted by the quick action of the testing staff (0.012% per test; 0.015% per individual patient). Only 1 patient (a 71yo M with severeCAD) required electrical cardioversion for ventricular fibrillation. None of the other patients, including all 6 women, presented with tachyarrhythmias. There were no deaths and no significant musculoskeletal trauma. Conclusion: Despite many patients with risk factors for cardiac and non-cardiac syncope in the cohort, syncope, and near-syncope with hemodynamic instability were very rare findings on guideline-directed GXTs.
Abstract 15304: Apical Ballooning Syndrome in the Setting of Severe Chronic Obstructive Pulmonary Disease Exacerbation
Authors: Christian Toquica Gahona, Sotirios Doukas, Abi Watts, Allan E Santos Argueta, Kavin Raj
Journal: Circulation (2022)

Apical ballooning syndrome (ABS), also known as Takotsubo cardiomyopathy, is a form of acute dilated cardiomyopathy associated with excessive catecholamine release. A 74-year-old female, chronic smoker with previously diagnosis of obstructive lung disease presented in the emergency department with severe shortness of breath and increase sputum production for the last 24hr. The patient was diagnosed with severe COPD exacerbation and received multiple doses of albuterol, methylprednisolone, ipratropium bromide/albuterol, and azithromycin. Despite this, the patient remained tachypneic and tachycardic with signs of impending respiratory failure. She was transferred to the ICU and intubated. After intubation, the patient received a continuous albuterol nebulizer, methylprednisolone, and ceftriaxone. A few hours later, the patient complained of chest pain, and EKG was done showing T wave inversion in lateral leads, troponin levels were 1.08 ng/mL (ULN 0.12ng/mL), and 2D Echo showed EF 50-55%, apical ballooning with dyskinesia, and inferior wall hypokinesis. Left heart catheterization showed non-obstructive coronary artery disease with 50% stenosis on the left anterior descending artery and distal ostial artery. Based on the previously recommended criteria, the diagnosis of the ABS was made. The patient had resolution of symptoms and echocardiogram findings after follow up. Although albuterol acts mainly on beta-2 receptors, cross-activation of beta-1 receptors can potentially lead to tachycardia. Previous case reports also support that excessive albuterol use in cases of asthma and COPD exacerbation may lead to ABS. This case may raise awareness that the extensive use of albuterol could have dramatic effects. Early switch to beta-2 agonist with higher specificity such as levalbuterol could be a reasonable approach in patients with severe COPD exacerbation.
Abstract 15397: Pericardial Delayed Hyperenhancement Predicts Outcomes in Idiopathic Recurrent Pericarditis
Authors: Alveena B Syed, Habib Layoun, Abdullah Yesilyaprak, Muhammad Majid, Ankit Agrawal, Muhammad M Furqan, Ashwin Kumar, Zachary S Yaker, Felix Berglund, Allan L Klein
Journal: Circulation (2022)

Introduction: Recurrent pericarditis (RP) is defined as recurrence of pericarditis after an initial documented episode of pericarditis and symptom free interval of four to six weeks. In this study, we aimed to investigate the prognostic value of the pericardial delayed hyperenhancement (DHE) in patients with idiopathic recurrent pericarditis (IRP). Hypothesis: We hypothesize that moderate to severe DHE is correlated with worse outcomes. Methods: Consecutive patients (n=223) with IRP from 2012-2019 were included. Out of 223 patients, 213 had DHE tracing. Patients were then followed for events of clinical improvement (CI), clinical remission (CR), and clinical recurrence. Results: The mean age of the 223 patients included was 45 ± 16 years, and 51% were females. DHE was divided into two groups none/mild (n=160) and moderate/severe (n=53). At baseline, median number of prior recurrences was 3 (Q1, Q3: 2,5). Furthermore, when adjusted for age, gender, prior number of recurrences, and anti-inflammatory therapy on multivariable cox-regression analysis, moderate to severe DHE was independently associated with less likelihood of having CI (HR 0.24, p&lt;0.001) and CR (HR 0.31, p=0.011), and more likelihood of having clinical recurrence (HR 1.58, p=0.02). On Kaplan Meier analysis, moderate to severe DHE was associated with more time to clinical improvement (log rank p&lt;0.0001), more time to clinical remission (log rank p&lt;0.0001), and less time to clinical recurrence (log rank p=0.0047). Conclusions: Moderate to severe DHE is independently correlated with worse outcomes in patients with IRP. DHE should be considered an important part of evaluation in patients with recurrent pericarditis and should be included in new guidelines. Our study will help clinicians utilize DHE as a prognostic marker in patients with IRP.
Abstract 15725: Non Existing Pacemaker: A Complication of Kyphoplasty
Authors: Nadim Ammari, Iuliia Kovalenko, Konstantin Golubykh, Aashay Patel
Journal: Circulation (2022)

Introduction: Diagnosis of cement emboli remains challenging due to heterogenicity of diagnostic findings. We describe a case of cement embolism interpreted as abandoned pacemaker leads. Case description: A 76-year-old female underwent lumbar kyphoplasty. In the post-anesthesia care unit, she developed multiple asymptomatic episodes of non-sustained ventricular tachycardia. Her lab work including basic metabolic panel, electrolytes, and troponin was unremarkable. A transthoracic echocardiogram (TTE) revealed intracardiac foreign body interpreted as abandoned pacemaker wires originating at the superior vena cava with one terminating in the right ventricular (RV) apex and the other in the right atrial (RA) appendage (Figure 1). Chest computer tomography (CT) confirmed intracardiac pacemaker wires. The patient denied any history of pacemaker placement. TTE and CT images were reviewed again with multiple other opinions stating that the foreign body represented dense cement from the vertebral body. It exited through a paravertebral vein into the inferior vena cava making its way to the right heart (Figure 2). Coronary angiography confirmed an elongated cement embolus. The patient underwent cement removal through sternotomy. Conclusions: Diagnosis of cement embolism may remain challenging as it can mimic any foreign bodies including pacemaker wires. Suspicion for the diagnosis should remain high in any patient who underwent kyphoplasty and developed cardiac arrhythmias or other cardiac symptoms. Image 1. A - Pacemaker lead passing through RA to the RV. Image 2. A- cement material in the right heart. B- Cement extravasating through right paravertebral vein.
Abstract 15649: Terf2ip K240 Sumoylation Drives Endothelial Senescence and Atherogenesis via Activating Parp1
Authors: Khanh Chau, Masaki Imanishi, Shengyu Li, Sivareddy Kotla, Kyung A Ko, Minh T Nguyen, Estefani Berrios Turcios, Rei Abe, Aijun Zhang, Elena McBeath, Keigi Fujiwara, Young Jin Gi, Kyung-Sun Heo, Jinke Cheng, Tamlyn Thomas, Keri Schadler, Anisha A Gupte, Ying H Shen, Steven Lin, Edward T Yeh, Keigi Fujiwra, Dale Hamilton, John P Cooke, Guangyu Wang, Junichi Abe, Nhat Tu Le, Yong Zuo, Amrish Sharma
Journal: Circulation (2022)

The goal of this study: Telomeric repeat-binding factor 2 (TRF2) interacting protein 1 (TERF2IP) not only associates with TRF2 to protect telomeres but also associates with RSK to promote senescence. The later has been detected in endothelial cells (ECs) under disturbed flow (DF), which involved TERF2IP S205 phosphorylation. Besides, it has been suggested that TERF2IP K240 can be SUMOylated; however, its role in senescence and atherogenesis remains unknown. Methods: We investigated the functional role of TERF2IP K240 SUMOylation utilizing a model of DF-induced atherogenesis in TERF2IP K237R knock-in (KI) (mouse K237 is equivalent to human K240) mouse carotid artery by partial ligation and RNA isolated from mouse lung ECs. Results: TERF2IP K240 SUMOylation was increased in ECs under DF and provoked telomere shortening-associated senescence. TERF2IP K240 SUMOylation occurred independently of TERF2IP S205 phosphorylation although both events were blunted by the RSK specific inhibitor (FMK-MEA), and EC senescence as well as related events were abolished by both depletion and point mutation of TERF2IP at S205 or K240 residue. Whereas point mutation of TERF2IP at S205 prevented RSK-associated NF-kB activation, that of K240 exhibited no effect, suggesting that K240 SUMOylation did not involve in EC inflammation. By inducing persistent telomere DNA damage, TERF2IP K240 SUMOylation distinctive provoked telomere shortening-associated EC senescence via inducing persistent DNA damage response and subsequent PARP1 activation. Finally, a mouse model of DF-induced atherogenesis showed that atherogenesis was inhibited in TER2IP K237R KI mice although body weight and cholesterol level were unaltered Discussions: These data have revealed that EC senescence plays a critical role in atherogenesis and that TERF2IP K240 SUMOylation can be a novel therapeutic target for atherogenesis.